Ethical, Legal, and Policy Best Practices

In addition to technical issues relating to the physical integrity and quality of biospecimens, multiple ethical, legal, and policy issues
should be considered in biospecimen research activities. Key ethical issues include respecting the autonomy of human research participants
(human subjects), protecting human research participants from breaches of privacy and confidentiality, and minimizing individual and group harms.
Legal and policy issues include adhering to relevant Federal, State, and local laws and regulations surrounding the collection, storage,
dissemination, and use of biospecimens; developing appropriate guidelines for biospecimen and associated data access; ensuring that biospecimens
are used in scientifically meritorious research; and establishing biospecimen resource governance (Refer to Sections
C1 through C6 for specific details about relevant regulations and policies).

In 2005, the NCI hosted a workshop that assembled diverse representatives from the cancer research community as well as ethics, legal, and policy
experts to discuss and propose approaches that could help unify, integrate, and improve NCI-supported biospecimen resources and biospecimen research
in general. The recommendations that resulted from this workshop as well as additional NCI-sponsored meetings and work conducted between 2002 and
2005 formed the basis of the NCI Best Practices, first published in 2007. The first revision to the NCI Best Practices, released
in 2011, provided additional recommendations formulated during the 2007 NCI-hosted Symposium-Workshop on
Custodianship and Ownership Issues in Biospecimen Research. Featuring leaders from the
academic community, private sector, patient advocacy groups, and Government agencies, this landmark symposium-workshop was convened to develop
recommendations for best practices concerning the custodianship of biospecimens and associated data at NCI-supported resources and to expand upon
the original NCI Best Practices in four key areas: (1) Considerations for human research participants, investigators, and institutions;
(2) financial conflicts of COIs; (3) intellectual property (IP); and (4) access to products and benefits. Recommendations generated during this
symposium-workshop comprise the 2011 revisions to Section C of the NCI Best Practices.

In this 2016 revision to the NCI Best Practices, the ethical, legal, and policy best practices have been updated based on more recent
guidance concerning informed consent, return of research results and incidental findings, and community engagement. In addition, corrections
and updates have been made to internet references for this growing area of research and policy.

Furthermore, investigators and biospecimen resources should consult their IRBs, as needed, and appropriate institutional officials to determine
how Federal and State regulations and policies would apply to their resource and how to implement recommendations in the NCI Best Practices related
to human subjects research as defined in 45 CFR Part 46. Biospecimen resources that expect to make samples available for NIH-funded research should
be aware of NIH data sharing policies [68]. In particular, if the samples will be used in an NIH-funded
project generating large-scale genomic data [69] , the NIH Genomic Data Sharing (GDS) Policy will apply
and the genomic data and accompanying phenotypic data are expected to be submitted to an NIH-designated data repository. The GDS Policy has set forth
expectations regarding informed consent [C.2], privacy and confidentiality [C.3], and access to data [C.3]. Therefore, to maximize the utility of
samples for NIH-funded research, biospecimen resources should anticipate that their sample collections will need to be consistent with NIH GDS Policy
requirements. An NIH-funded project falls under the GDS Policy due to the type of data that it generated. The samples used in the project may come
from a variety of sources, including biospecimen resources who are not otherwise actively involved in the project. For example, the investigators
may have contacted a biobank known to have relevant samples, and obtained them through a standardized process. Another example is when the
investigators reach out to a researcher who has been maintaining a sample collection in a lab, and asks them to be a collaborator and provide
those samples through an MTA mechanism.

As part of GDS Policy compliance, the project’s principal investigator and institution must provide assurance for several steps in the research
process. While this institution can assure that an IRB considered the risks of submission to an NIH-designated repository, and reviewed the
investigator’s plan for de-identifying the dataset consistent with the GDS, the institution may not feel comfortable attesting to aspects
of the research process that occurred outside of the project and beyond the institution. These are typically the points in the institutional
certification template that relate to the sample collection and informed consent:

Any limitations on the research use of the data, as expressed in the informed consent documents, are delineated;

An IRB, privacy board, and/or equivalent body, as applicable, has reviewed the investigator’s proposal for data submission and assures that:

The protocol for the collection of genomic and phenotypic data is consistent with 45CFR Part 46;

Data submission and subsequent data sharing for research purposes are consistent with the informed consent of study participants from whom the data were obtained;

As such, biospecimen resources who have engaged with researchers whose projects fall under the GDS policy should be prepared to support the
institutional certification process. It may be they will be asked to provide a statement/memorandum attesting to the points above, where appropriate.
If the biospecimen resource is not able to attest to the points (e.g. when they did not collect the samples themselves), then the resource should
be prepared to put the investigator in touch with the original sample source.

It will be most helpful to the institutional certification process if the biospecimen resource keeps records of the permitted future research use
for the samples. Permitted future research uses should be included in any supporting documentation, as these will become the data use limitations
used by an NIH Data Access Committee to determine which secondary researchers can access the data.

The ethical, legal, and policy best practices outlined in this document identify key regulations and recommendations relevant to biospecimen
collection, storage, dissemination, and use in research. These best practices are more detailed and extensive than, for example, a grant policy
statement; however, not every element outlined in the NCI Best Practices would apply to every biospecimen research activity. Investigators
and biospecimen resource directors should consider these principles carefully in conjunction with the objective of the research project and the
mission of the biospecimen resource to determine the most appropriate operational policies. Furthermore, investigators and biospecimen resources
should consult their IRBs, as needed, and appropriate institutional officials to determine how Federal and State regulations and policies would
apply to their resource and how to implement recommendations in the NCI Best Practices related to human subjects research, as defined in
45 CFR Part 46 [70].

The regulations and proposed standards discussed in this document are for research using biospecimens in the United States. Many countries
have their own ethical, legal and policy standards for human subjects research including, in some cases, specific provisions for the use of
biospecimens. Investigators and biospecimen resources should be aware of international standards that may be applicable and address any
differences between international and U.S. regulatory requirements prior to the initiation of a new collaboration or collection.